TGF‐β‐mediated exosomal lnc‐MMP2‐2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression

Abstract

Previous studies indicated that transforming growth factor (TGF)‐β‐mediated exosomal microRNAs (miRNAs) regulate the migration and invasion of lung cancer cells; however, whether and how TGF‐β‐mediated exosomal long noncoding (lnc) RNAs regulate migration and invasion of lung cancer cells remains unclear. Here, coculture experiments showed that TGF‐β pretreatment increased the migration and invasion potential of lung cancer cells and TGF‐β pretreated A549 cells increases vascular permeability. Furthermore, we found that TGF‐β‐mediated exosomes, as carriers of intercellular communication, regulated lung cancer invasion, and vascular permeability. Transcriptional analysis also revealed that lnc‐MMP2‐2 was highly enriched in TGF‐β‐mediated exosomes and might function by increasing the expression of matrix metalloproteinase (MMP)2 through its enhancer activity, with ectopic expression and silencing of lnc‐MMP2‐2 affecting lung cancer invasion and vascular permeability. Additionally, lnc‐MMP2‐2 and MMP2 expression was assessed semiquantitatively, and tissue‐specific correlations between lnc‐MMP2‐2 and MMP2 expression were evaluated. These results suggested that exosomal lnc‐MMP2‐2 might regulate the migration and invasion of lung cancer cells into the vasculature by promoting MMP2 expression, suggesting this lncRNA as a novel therapeutic target and predictive marker of tumor metastasis in lung cancer.